Abstract
Aquaporins (AQPs) are small transmembrane tetrameric proteins that facilitate water, solute and gas exchange. Their presence has been extensively reported in the biological membranes of almost all living organisms. Although their discovery is much more recent than ion transport systems, different biophysical approaches have contributed to confirm that permeation through each monomer is consistent with closed and open states, introducing the term gating mechanism into the field. The study of AQPs in their native membrane or overexpressed in heterologous systems have experimentally demonstrated that water membrane permeability can be reversibly modified in response to specific modulators. For some regulation mechanisms, such as pH changes, evidence for gating is also supported by high-resolution structures of the water channel in different configurations as well as molecular dynamics simulation. Both experimental and simulation approaches sustain that the rearrangement of conserved residues contributes to occlude the cavity of the channel restricting water permeation. Interestingly, specific charged and conserved residues are present in the environment of the pore and, thus, the tetrameric structure can be subjected to alter the positions of these charges to sustain gating. Thus, is it possible to explore whether the displacement of these charges (gating current) leads to conformational changes? To our knowledge, this question has not yet been addressed at all. In this review, we intend to analyze the suitability of this proposal for the first time.
Original language | English |
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Article number | 12317 |
Journal | International Journal of Molecular Sciences |
Volume | 23 |
Issue number | 20 |
DOIs | |
State | Published - 2022 |
Bibliographical note
Funding Information:This research was funded by the National Agency for Research and Development (ANID) through the following programs: The Fondecyt grant N° 1221260 was awarded to J.A.G. The CINV and Millennium Nucleus in Nano Biophysics are funded by the Millennium Science Initiative Program ICM-ANID through grants ICN09-022 (C.G. and J.A.G.) and NCN2021_021 (J.A.G.). Center Science and Life, Basic Financing for Scientific and Technologic Centres of Excellence ANID FB210008, (J.A.G.) and by National Committee of Scientific and Technologic Research (CONICYT)/Advanced Human Capital Formation Program/National Doctorate/2017-21171141 to M.F, 2019-21200727 to J.J.A.-A., 2019-21200754 to C.C. and 2019-21191239 to A.P.-P. This research was also funded by FONCYT grants number BID PICT14 0744 and PICT17 2338 (to G.A.), PICT17 0368 (to M.O.) and by the University of Buenos Aires grants number UBACyT18-20 20020170100314BA (to G.A.) and 20020170200049BA (to M.O.). E.M.C. is a PEW Latin American Fellow.
Publisher Copyright:
© 2022 by the authors.
ASJC Scopus subject areas
- Catalysis
- Molecular Biology
- Spectroscopy
- Computer Science Applications
- Physical and Theoretical Chemistry
- Organic Chemistry
- Inorganic Chemistry